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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Dental pain induced by an ambient thermal differential: pathophysiological hypothesis

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          Abstract

          Dental pain triggered by temperature differential is a misrecognized condition and a form of dental allodynia. Dental allodynia is characterized by recurrent episodes of diffuse, dull and throbbing tooth pain that develops when returning to an indoor room temperature after being exposed for a long period to cold weather. The pain episode may last up to few hours before subsiding. Effective treatment is to properly shield the pulpal tissue of the offending tooth by increasing the protective layer of the dentin/enamel complex. This review underscores the difference in dentin hypersensitivity and offers a mechanistic hypothesis based on the following processes. Repeated exposure to significant positive temperature gradients (from cold to warm) generates phenotypic changes of dental primary afferents on selected teeth with subsequent development of a “low-grade” neurogenic inflammation. As a result, nociceptive C-fibers become sensitized and responsive to innocuous temperature gradients because the activation threshold of specific TRP ion channels is lowered and central sensitization takes place. Comprehensive overviews that cover dental innervation and sensory modalities, thermodynamics of tooth structure, mechanisms of dental nociception and the thermal pain are also provided.

          Most cited references32

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          Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors.

          The transient receptor potential (TRP) superfamily of cation channels contains four temperature-sensitive channels, named TRPV1-4, that are activated by heat stimuli from warm to that in the noxious range. Recently, two other members of this superfamily, TRPA1 and TRPM8, have been cloned and characterized as possible candidates for cold transducers in primary afferent neurons. Using in situ hybridization histochemistry and immunohistochemistry, we characterized the precise distribution of TRPA1, TRPM8, and TRPV1 mRNAs in the rat dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons. In the DRG, TRPM8 mRNA was not expressed in the TRPV1-expressing neuronal population, whereas TRPA1 mRNA was only seen in some neurons in this population. Both A-fiber and C-fiber neurons expressed TRPM8, whereas TRPV1 was almost exclusively seen in C-fiber neurons. All TRPM8-expressing neurons also expressed TrkA, whereas the expression of TRPV1 and TRPA1 was independent of TrkA expression. None of these three TRP channels were coexpressed with TrkB or TrkC. The TRPM8-expressing neurons were more abundant in the TG compared with the DRG, especially in the mandibular nerve region innervating the tongue. Our data suggest heterogeneity of TRPM8 and TRPA1 expression by subpopulations of primary afferent neurons, which may result in the difference of cold-sensitive primary afferent neurons in sensitivity to chemicals such as menthol and capsaicin and nerve growth factor. Copyright (c) 2005 Wiley-Liss, Inc.
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            Guidelines for the design and conduct of clinical trials on dentine hypersensitivity.

            Clinical trials on dentine hypersensitivity have been numerous and protocols varied. To date there is little consensus as to the conduct of studies on this poorly-understood yet common and painful dental condition. A committee of interested persons from academia and industry was convened to discuss the subject of clinical trials on dentine hypersensitivity and a consensus report is presented. A double-blind randomized parallel groups design is recommended, although cross-over designs may be used for the preliminary screening of agents. Subjects may have multiple sites scored. Sample size will be determined by estimating the variability in the study population, the effect to be detected and the power of the statistical test to be used. Subject selection is based on a clinical diagnosis of dentine hypersensitivity, excluding those with conflicting characteristics such as currently-active medical or dental therapy. The vestibular surfaces of incisors, cuspids and bicuspids are preferred as sites to be tested. A range of sensitivity levels should be included. Tactile, cold and evaporative air stimuli should be applied. Negative and benchmark controls should be incorporated. Most trials should last 8 weeks. Sensitivity may be assessed either in terms of the stimulus intensity required to evoke pain or the subjective evaluation of pain produced by a stimulus using a visual analog or other appropriate scale. The subject's overall assessment may be determined by questionnaire. Outcomes should be expressed in terms of clinically significant changes in symptoms. Follow-up evaluation is required to determine the persistence of changes. At least 2 independent trials should be conducted before a product receives approval.
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              Thermosensation and pain.

              We feel a wide range of temperatures spanning from cold to heat. Within this range, temperatures over about 43 degrees C and below about 15 degrees C evoke not only a thermal sensation, but also a feeling of pain. In mammals, six thermosensitive ion channels have been reported, all of which belong to the TRP (transient receptor potential) superfamily. These include TRPV1 (VR1), TRPV2 (VRL-1), TRPV3, TRPV4, TRPM8 (CMR1), and TRPA1 (ANKTM1). These channels exhibit distinct thermal activation thresholds (>43 degrees C for TRPV1, >52 degrees C for TRPV2, > approximately 34-38 degrees C for TRPV3, > approximately 27-35 degrees C for TRPV4, < approximately 25-28 degrees C for TRPM8 and <17 degrees C for TRPA1), and are expressed in primary sensory neurons as well as other tissues. The involvement of TRPV1 in thermal nociception has been demonstrated by multiple methods, including the analysis of TRPV1-deficient mice. TRPV2, TRPM8, and TRPA1 are also very likely to be involved in thermal nociception, because their activation thresholds are within the noxious range of temperatures.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2017
                15 December 2017
                : 10
                : 2845-2851
                Affiliations
                [1 ]Laboratory of Neurosciences of Brest (EA4685), University of Western Brittany, Brest, France
                [2 ]Dental School, University of Western Brittany, Brest, France
                [3 ]Assessment and Treatment Center of Pain, Regional and University Hospital Center, Brest, France
                [4 ]Laboratory IRDL, FRE CNRS 3744, University of Western Brittany, Brest, France
                [5 ]School of Dental Medicine, Universite Laval, Quebec, QC, Canada
                Author notes
                Correspondence: Anaïs Le Fur-Bonnabesse, Faculté d’odontologie, Université de Bretagne Occidentale, 22, Avenue Camille Desmoulins – CS93837, 29200 Brest, France, Tel +33 2 9801 6489, Fax +33 2 9801 6932, Email anais.lefurbonnabesse@ 123456univ-brest.fr
                Article
                jpr-10-2845
                10.2147/JPR.S142539
                5736355
                29290692
                bc541933-e28d-457f-8280-a9bda8e43da7
                © 2017 Le Fur-Bonnabesse et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Anesthesiology & Pain management
                pain,dental pain,thermal allodynia,atypical tooth sensitivity,dentin hypersensitivity

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